Abstract 16708: Increasing Age and the Benefit From Higher-intensity Lipid Lowering With Ezetimibe/Simvastatin vs. Simvastatin Alone: Results From the IMPROVE-IT Trial
Introduction: While lipid lowering reduces cardiovascular (CV) events, evidence supporting high-intensity lipid lowering among elderly pts is more limited, and recent guidelines recommend moderate rather than high-intensity therapy for pts >75 yrs. We explored age subgroups within the IMPROVE-IT trial to evaluate whether age modified the benefit of adding ezetimibe (EZ) to statin therapy.
Methods and Results: The IMPROVE-IT trial demonstrated the combination of EZ and simvastatin (EZ/S) significantly reduced major CV events vs. simvastatin (S) alone in pts with acute coronary syndrome (ACS) and LDL-C between 50 and 125 mg/dL. The primary composite endpoint was CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, and coronary revascularization >30 days. Outcomes according to age were compared in pre-specified subgroups using Kaplan-Meier (KM) analysis and Cox proportional hazards models using age as a continuous variable. Of the 18,144 pts enrolled, 7971 (44%) were 65 yrs or older and 2798 (15%) were 75 yrs or older at randomization. As age increased, event rate increased with KM rates at 7 yrs in the S arm of 30.8% for pts <65 yrs, 39.9% for pts ≥65 yrs, and 47.6% for pts ≥75 yrs. Treatment with EZ/S compared with S resulted in lower event rates in all age groups with an absolute reduction for pts <65 yrs of 0.85% (HR 0.98 CI 0.90-1.05), for pts ≥65 yrs of 3.6% (HR 0.89 CI 0.82-0.96), and for pts ≥75 yrs of 8.7% (HR 0.80 CI 0.70-0.90), with interaction P values of 0.09 and 0.005, respectively. Using age as a continuous variable found event rates for EZ/S vs. S were always lower, but the test for interaction between age and treatment effect for the primary endpoint was non-significant (P=0.15). The rate of gallbladder, liver, and muscle-related adverse events was not increased with EZ/S vs. S among older pts or younger pts.
Conclusions: In the IMPROVE-IT trial, pts 65 yrs or older and especially pts 75 yrs or older after ACS derived substantial benefit from higher-intensity lipid lowering therapy with EZ/S compared with S alone, with no increase in safety issues among older age subgroups. These results may have implications for guideline recommendations regarding more intensive lipid lowering in the elderly.
Author Disclosures: R.G. Bach: Research Grant; Modest; AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Merck, Volcano. Consultant/Advisory Board; Modest; Eli Lilly (Clinical Event Committee activity only), Pfizer (Clinical Event Committee activity only). Consultant/Advisory Board; Significant; Novo Nordisk (Clinical Event Committee activity only). C. Cannon: Research Grant; Significant; Accumetrics, Arisaph, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janssen, Merck, Takeda. Consultant/Advisory Board; Modest; Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, Takeda, CSL Behring, Essentials, Kowa, Pfizer, GlaxoSmithKline. Consultant/Advisory Board; Significant; Lipimedix, Regeneron, Sanofi. R. Giugliano: Honoraria; Modest; Merck. Consultant/Advisory Board; Modest; Amgen, GlaxoSmithKline, Merck, Portola, American College of Cardiology, CVS Caremark. Other; Modest; St Jude Medical. Research Grant; Significant; Amgen, Merck. Other; Significant; Lexicon. J. White: None. Y. Lokhnygina: None. A. Tershakovec: Employment; Significant; Merck (employee, stockholder, holds stock options). T. Musliner: Employment; Significant; Merck (Former employee & stockholder). E. Braunwald: Research Grant; Significant; Daiichi Sankyo, GlaxoSmithKline, Bristol-Myers Squibb, Duke University, AstraZeneca, Johnson & Johnson, Sanofi Aventis, Merck. Speakers Bureau; Modest; Merck. Speakers Bureau; Significant; Daiichi Sankyo, Menarini International, Bayer, Medscape, Novartis. Consultant/Advisory Board; Modest; Sanofi Aventis, The Medicines Company, Merck. M. Blazing: Consultant/Advisory Board; Modest; AstraZeneca, Pfizer, Merck&Co., Inc, Pfizer, Regeneron, Sanofi. Research Grant; Significant; sanofi, Merck & Co. Honoraria; Significant; Merck&Co. Consultant/Advisory Board; Significant; Merck & Co.
- © 2015 by American Heart Association, Inc.